Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy

Cancers

Vincenzo Cerullo¹  Sara Feola¹  Karita Peltonen¹  Jacopo Chiaro¹  Erkko Ylösmäki¹  Rui M. M. Branca²  Husen M. Umer²  Janne Lehtiö²  Georgios Mermelekas²  Sari Pesonen³ 

[1] Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland;Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Solna, Sweden;Valo Therapeutics Oy, 00790 Helsinki, Finland;

关键词: tumor antigen;    endogenous retrovirus;    cancer vaccine;    immunotherapy;    immunopeptidome;    ligandome;   

DOI  :  10.3390/cancers13143408

来源: DOAJ

【 摘 要 】

Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interrogating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexible and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating immunopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.

【 授权许可】

Unknown